Anticoagulation in Patients with Chronic Kidney Disease.

BACKGROUND: Both atrial fibrillation and venous thromboembolism (VTE) are highly prevalent among patients with chronic kidney disease (CKD). Until recently, warfarin was the most commonly prescribed oral anticoagulant. Direct oral anticoagulants (DOACs) have important advantages and have been shown to be noninferior to warfarin with respect to stroke prevention or recurrent VTE in the general population, with lower bleeding rates. This review article will provide available evidence on the use of DOACs in patients with CKD. SUMMARY: In post hoc analyses of major randomized studies with DOACs for stroke prevention in atrial fibrillation, in the subgroup of participants with moderate CKD, defined as a creatinine clearance (CrCl) of 30-50 mL/min, dabigatran 150 mg and apixaban were associated with lower rates of stroke and systemic embolism, whereas apixaban and edoxaban were associated with lower bleeding and mortality rates, compared with warfarin. In retrospective observational studies in patients with advanced CKD (defined as a CrCl <30 mL/min) and atrial fibrillation, DOACs had similar efficacy with warfarin with numerically lower bleeding rates. All agents warrant dose adjustment in moderate-to-severe CKD. In patients on maintenance dialysis, the VALKYRIE trial, which was designed initially to study the effect of vitamin K on vascular calcification progression, established superiority for rivaroxaban compared with a vitamin K antagonist (VKA) in the extension phase. Two other clinical trials using apixaban (AXADIA and RENAL-AF) in this population were inconclusive due to recruitment challenges and low event rates. In post hoc analyses of randomized studies with DOACs in patients with VTE, in the subgroup of participants with moderate CKD at baseline, edoxaban was associated with lower rates of recurrent VTE, whereas rivaroxaban and dabigatran were associated with lower and higher bleeding rates, respectively, as compared to warfarin. KEY MESSAGES: DOACs have revolutionized the management of atrial fibrillation and VTE, and they should be preferred over warfarin in patients with moderate-to-severe CKD with appropriate dose adjustment. Therapeutic drug monitoring with a valid technique may be considered to guide clinical management in individualized cases. Current evidence questions the need for oral anticoagulation in patients on maintenance dialysis with atrial fibrillation as both DOACs and VKAs are associated with high rates of major bleeding.

Clinical Outcomes of Left Bundle Branch Area Pacing Compared with Biventricular Pacing in Patients with Heart Failure Requiring Cardiac Resynchronization Therapy: Systematic Review and Meta-Analysis.

Background: Biventricular pacing (BVP) is recommended for patients with heart failure (HF) who require cardiac resynchronization therapy (CRT). Left bundle branch area pacing (LBBAP) is a novel pacing strategy that appears to ensure better electrical and mechanical synchrony in these patients. Our aim was to systematically review and meta-analyze the existing evidence regarding the clinical outcomes of LBBAP-CRT compared with BVP-CRT. Methods: Medline, Embase, Cochrane Central Register of Controlled Trials and Web of Science databases were searched for studies comparing LBBAP-CRT with BVP-CRT. Outcomes were all-cause mortality, heart failure hospitalizations (HFH) and New York Heart Association (NYHA) class improvement. We included randomized controlled trials (RCTs) and observational studies with participants that had left ventricular ejection fraction (LVEF) ≤ 40% and (i) symptomatic HF or (ii) expected ventricular pacing > 40%. Random and fixed effects models pairwise meta-analysis was conducted. Cochrane Risk of Bias 2 assessment tool (ROB 2.0) and the Newcastle-Ottawa scale (NOS) were used to assess the quality of the studies. Results: Eleven studies (10 observational studies and 1 RCT) with 3141 patients were included in the analysis. Compared with BVP-CRT, LBBAP-CRT was associated with lower risk of all-cause mortality (risk ratio (RR): 0.71, 95% CI: 0.57 to 0.87; p = 0.001), lower risk of HFH (RR: 0.59, 95% CI: 0.50 to 0.71; p < 0.00001) and more improvement in NYHA class (weighed mean difference (WMD): -0.36, 95% CI: -0.59 to -0.13; p < 0.00001) compared with patients who received BVP-CRT. Conclusions: Compared with BVP-CRT, receipt of LBBAP-CRT in patients with HF is associated with a lower risk of mortality, and HFH and greater improvement in NHYA class.

Prediction of incident chronic kidney disease in community-based electronic health records: a systematic review and meta-analysis.

Background: Chronic kidney disease (CKD) is a major global health problem and its early identification would allow timely intervention to reduce complications. We performed a systematic review and meta-analysis of multivariable prediction models derived and/or validated in community-based electronic health records (EHRs) for the prediction of incident CKD in the community. Methods: Ovid Medline and Ovid Embase were searched for records from 1947 to 31 January 2024. Measures of discrimination were extracted and pooled by Bayesian meta-analysis, with heterogeneity assessed through a 95% prediction interval (PI). Risk of bias was assessed using Prediction model Risk Of Bias ASsessment Tool (PROBAST) and certainty in effect estimates by Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results: Seven studies met inclusion criteria, describing 12 prediction models, with two eligible for meta-analysis including 2 173 202 patients. The Chronic Kidney Disease Prognosis Consortium (CKD-PC) (summary c-statistic 0.847; 95% CI 0.827-0.867; 95% PI 0.780-0.905) and SCreening for Occult REnal Disease (SCORED) (summary c-statistic 0.811; 95% CI 0.691-0.926; 95% PI 0.514-0.992) models had good model discrimination performance. Risk of bias was high in 64% of models, and driven by the analysis domain. No model met eligibility for meta-analysis if studies at high risk of bias were excluded, and certainty of effect estimates was 'low'. No clinical utility analyses or clinical impact studies were found for any of the models. Conclusions: Models derived and/or externally validated for prediction of incident CKD in community-based EHRs demonstrate good prediction performance, but assessment of clinical usefulness is limited by high risk of bias, low certainty of evidence and a lack of impact studies.

Safety and efficacy of left bundle branch area pacing compared with right ventricular pacing in patients with bradyarrhythmia and conduction system disorders: Systematic review and meta-analysis.

BACKGROUND: Right Ventricular Pacing (RVP) may have detrimental effects in ventricular function. Left Bundle Branch Area Pacing (LBBAP) is a new pacing strategy that appears to have better results. The aim of this systematic review and meta-analysis is to compare the safety and efficacy of LBBAP vs RVP in patients with bradyarrhythmia and conduction system disorders. METHODS: MEDLINE, EMBASE and Pubmed databases were searched for studies comparing LBBAP with RVP. Outcomes were all-cause mortality, atrial fibrillation (AF) occurrence, heart failure hospitalizations (HFH) and complications. QRS duration, mechanical synchrony and LVEF changes were also assessed. Pairwise meta-analysis was conducted using random and fixed effects models. RESULTS: Twenty-five trials with 4250 patients (2127 LBBAP) were included in the analysis. LBBAP was associated with lower risk for HFH (RR:0.33, CI 95%:0.21 to 0.50; p < 0.001), all-cause mortality (RR:0.52 CI 95%:0.34 to 0.80; p = 0.003), and AF occurrence (RR:0.43 CI 95%:0.27 to 0.68; p < 0.001) than RVP. Lead related complications were not different between the two groups (p = 0.780). QRSd was shorter in the LBBAP group at follow-up (WMD: -32.20 msec, CI 95%: -40.70 to -23.71; p < 0.001) and LBBAP achieved better intraventricular mechanical synchrony than RVP (SMD: -1.77, CI 95%: -2.45 to -1.09; p < 0.001). LBBAP had similar pacing thresholds (p = 0.860) and higher R wave amplitudes (p = 0.009) than RVP. CONCLUSIONS: LBBAP has better clinical outcomes, preserves ventricular electrical and mechanical synchrony and has excellent pacing parameters, with no difference in complications compared to RVP.